Locally ablative treatment of breast cancer liver metastases: identification of factors influencing survival (the Mammary Cancer Microtherapy and Interventional Approaches (MAMMA MIA) study)

Max Seidensticker, Benjamin Garlipp, Sophia Scholz, Konrad Mohnike, Felix Popp, Ingo Steffen, Ricarda Seidensticker, Patrick Stübs, Maciej Pech, Maciej PowerskI, Peter Hass, Serban-Dan Costa, Holger Amthauer, Christiane Bruns, Jens Ricke

Liver metastases from breast cancer (LMBC) are typically considered to indicate systemic disease spread and patients are most often offered systemic palliative treatment only. However, retrospective studies suggest that some patients may have improved survival with local treatment of their liver metastases compared to systemic therapy alone. In the absence of randomized trials, it is important to identify patient characteristics indicating that benefit from local treatment can be expected. 59 patients undergoing radiofrequency ablation (RFA), interstitial brachytherapy (BT), or radioembolization (RE) of LMBC as a salvage treatment were studied. Potential factors influencing survival were analyzed in a multivariate Cox model. For factors identified to have an independent survival impact, Kaplan-Meier analysis and comparison of overall survival (OS) using the log-rank test was performed. Median OS following local interventional treatment was 21.9 months. Considering only factors evaluable at treatment initiation, maximum diameter of liver metastases (≥3.9 cm; HR: 3.1), liver volume (≥ 1376 mL; HR: 2.3), and history of prior chemotherapy (≥ 3 lines of treatment; HR: 2.5-2.6) showed an independent survival impact. When follow-up data were included in the analysis, significant factors were maximum diameter of liver metastases (≥ 3.9 cm; HR: 3.1), control of LMBC during follow-up (HR: 0.29), and objective response as best overall response (HR: 0.21). Neither the presence of any extrahepatic metastases nor presence of bone metastases only had a significant survival impact. Median OS was 38.7 vs. 16.1 months in patients with metastases < vs. ≥ 3.9 cm, 36.6 vs. 10.2 months for patients having objective response vs. stable/progressive disease, and 38.5 vs. 14.2 months for patients having controlled vs. non-controlled disease at follow-up. Local control of LMBC confers a survival benefit and local interventional treatment for LMBC should be studied in a randomized trial. Patients with small metastases and limited history of systemic LMBC treatment are most likely to benefit from local approaches. Limited extrahepatic disease should not lead to exclusion from a randomized study and should not be a contraindication for local LMBC treatment as long as no randomized data are available.